Baby Sam's rash is mimicking measles

With the contagious culprit ruled out, what was the real cause of this infant’s rash?
maculopapular-rash

Sam, aged 12 months, was brought into the ED by his parents with a two-day history of rash, associated with a five-day history of fever, coryzal symptoms and decreased food intake.

There was no associated cough. Two days before the onset of the fever, Sam had received his 12-month MMR, haemophilus influenzae type b and meningococcal C vaccinations.1

He had last attended childcare two weeks before presentation. There was no significant history of travel or infectious contacts. His past medical history was unremarkable; he was born at term and was meeting developmental milestones.

On examination, Sam was alert but irritable. He had a fever of 38.9°C, but his other vital signs were within normal range.

Initial examination revealed a maculopapular rash, largely involving the legs and buttocks and extending to the abdomen, trunk and back (see image above). He had palpable cervical lymphadenopathy (≤1cm nodes), with no signs of otitis media or Koplik’s spots. 

Management

Sam was admitted to hospital for exclusion of measles and observation. Investigations revealed a neutrophilia at 12.14 x 109L (normal 1.25-7.50 x 109L), a mild lymphopenia at 2.84 x 109L (normal 4.75-10.00 x 109L) and an elevated CRP of 158mg/L (normal is less than 5mg/L). Nose and throat swabs for measles RNA were negative.

The following day, further questioning revealed Sam had had bilateral non-purulent conjunctivitis since the onset of the fever. Additional examination confirmed the previous assessment findings and the bilateral non-purulent conjunctivitis, with an erythematous oropharynx. 

Diagnosis

Sam was diagnosed with Kawasaki disease and was treated with IV immunoglobulin (IVIg) and aspirin.

The rash, fever and lymphadenopathy resolved within three days of IVIg administration.

After discharge, close outpatient follow-up for cardiovascular complications was arranged. 
 

Box 1. The Diagnostic Criteria for Kawasaki Disease
MUST HAVE: Fever for five days

Plus 

Four of the following five cardinal criteria:
  1. Erythema of oral and/or pharyngeal mucosa, characteristic ‘strawberry tongue’,
    reddened/cracked lips
     
  2. Bilateral conjunctival injection without exudate
     
  3. Maculopapular, diffuse erythroderma, or erythema multiforme-like rash
    
  4. Change in extremities
        Acute: erythema and/or oedema of hands, feet
        Subacute: periungual desquamation
     
  5. Cervical lymphadenopathy (often unilateral with node size >1.5cm)

Exclusion of other diseases with similar findings including streptococcal infection
(eg, scarlet fever), staphylococcal infection (eg, scaled skin syndrome), measles,
Steven Johnson syndrome, drug reaction, and juvenile rheumatoid arthritis.

Source: Circulation 2017; 135:e927-99.


Discussion

Fever and maculopapular rash in an unwell and non-immune child should raise suspicion of measles.

Measles is classically characterised by cough, conjunctivitis and a maculopapular rash involving the face and neck and extending downwards.

Measles is an acute viral illness spread by airborne droplets, aerosol and direct contact and is highly infectious via the respiratory route.3 

Measles infection contracted prior to vaccination was a possible cause of Sam’s presentation, given the typical incubation period is 7-18 days.4

However, a facial-sparing rash and the absence of cough would be unusual for measles. Importantly, there were no reported cases in the community at that time, and swabs for measles RNA were negative.

Measles vaccine reaction, which typically presents 7-10 days post-vaccination, with malaise and/or rash that is non-infectious, was also considered in this infant.1

While most viral exanthema in infants seen in daily practice are self-limiting and do not require further investigation or treatment, paediatric or ED referral should be initiated if the fever fails to improve at seven days without explanation or at five days if at least one additional criterion of Kawasaki disease is present.

When patients present to general practices or EDs with suspected measles, infection control measures should be initiated as soon as practicable. This includes droplet and contact precautions, including separating the index patient from other patients in the waiting room. 

For patients who are referred to an ED, it is important to forewarn the department to prepare to divert the patient to a negative–pressure room rather than waiting in the triage area.4 

Measles is investigated by collecting nose and throat PCR swabs for measles RNA. Sensitivity is highest 1-3 days after rash onset, but the virus can be detected up to 10-14 days later.5 Measles-specific IgM and IgG antibodies are not useful in patients who have received measles vaccine within eight days to eight weeks prior to testing.4 

Obtain blood cultures in cases where bacteraemia cannot be excluded clinically. 

Kawasaki disease is a systemic vasculitis affecting medium-sized arteries, including coronary arteries. It mainly affects children under five. Diagnosis is based on clinical features.

Incomplete Kawasaki disease, where all diagnostic criteria are not met, may also occur.8 Early recognition is important because of the potential for long-term cardiac complications. Suspected cases require hospital admission.

Without treatment, 25% of affected patients develop coronary artery aneurysms.6 Other cardiovascular complications include acute thrombosis, long-term risk of myocardial ischaemia, pericardial effusion, valvular regurgitation, myocarditis and ventricular dysfunction.

The condition is treated with IVIg. This should ideally be given within 10 days of fever onset to reduce the risk of cardiac complications, especially coronary artery aneurysms.6

Moderate-to-high-dose aspirin — switched to a lower dose once the patient is afebrile for 48 hours and continued for a minimum of 4-6 weeks following acute phase treatment — is recommended.

However, there is no evidence that aspirin reduces coronary artery aneurysms.2 High-risk and IVIg-resistant cases may benefit from adjunctive therapies, including corticosteroids and infliximab.2,7,8 

For uncomplicated patients, serial echocardiograms are recommended. These are performed at presentation and repeated both within 1-2 weeks and 4-6 weeks after treatment to monitor for coronary sequelae.2

Key messages
  • Fever and rash in an unwell infant require close monitoring. Consider paediatric referral especially if failing to improve.
  • Measles is a consideration in non-immune children, especially if associated with dry cough, coryza, conjunctivitis and maculopapular rash. Place non-immune children with suspected measles in airborne droplet and contact precautions until measles is excluded.
  • Consider Kawasaki disease in infants with fever persisting for at least five days with four of the five cardinal features. Treatment during the first ten days of illness reduces the cardiovascular complications.

Dr Peter Chisholm and Dr Alisara Suknate are medical registrars.

Dr Lyn-li Lim is an infectious diseases physician.

Dr Alice Fang is a paediatrician and neonatologist.

References on request.